Efficacy of mycophenolate mofetil combined with topical 0.05%tacrolimus in high-risk keratoplasty:1-year cohort study

AIM:To investigate the efficacy of systemic mycophenolate mofetil(MMF)as an adjunct in combination with topical tacrolimus(FK506)and corticosteroid eyedrops for preventing corneal graft rejection after high-risk keratoplasty(HRK).METHODS:In this cohort study,55 consecutive patients(55 eyes)from an eye center who met the criteria of HRK were included.The definition for HRK includes large grafts of no less than 9 mm diameter,vascularized cornea of two or more quadrants,regrafting,or eccentric grafts.After penetrating keratoplasty,25 patients treated with systemic MMF in combination with 0.05%FK506 and tapering corticosteroid eyedrops were enrolled in Group 1 from October 2019.Thirty patients receiving postoperative treatment with 0.05%FK506 and tapering corticosteroid eyedrops alone were enrolled in Group 2 from January 2018 to September 2019.All participants were closely monitored after surgery,and episodes of graft rejection and relevant clinical data were collected and assessed over a one-year follow-up period.RESULTS:After a follow-up of 9.6±3.2mo,graft rejection episodes occurred in 4 cases(16%)in Group 1 and 18 cases(60%)in Group 2.One reversible and 3 irreversible graft rejections occurred in Group 1,while 3 reversible and 15 irreversible rejections occurred in Group 2.Kaplan-Meier analysis revealed that 82.5%of grafts in Group 1 and 37.1%in Group 2 did not experience corneal graft rejection(P<0.01,log-rank test).The clear graft survival rate was 83.6%in Group 1 and 36.7%in Group 2(P<0.01,log-rank test)within one year of follow-up.No severe systemic side effects were observed in either group during the follow-up period.CONCLUSION:The triple treatment regimen consisting of MMF,topical FK506,and corticosteroid eyedrops represents a promising strategy for effectively preventing graft rejection and improving graft survival in patients with HRK.

Combination treatment with telitacicept,mycophenolate mofetil and glucocorticoids for immunoglobulin A nephropathy:A case report

BACKGROUND Telitacicept reduces B cell activation and abnormal immunoglobulin A(IgA)antibody production by inhibiting the activity of B lymphocyte stimulator(BLyS)and a proliferation-inducing ligand(APRIL),thereby decreasing IgA deposition in the glomeruli and local inflammatory response.This ultimately protects the kidneys from damage.This mechanism suggests that Telitacicept has potential efficacy in the treatment of IgA nephropathy.CASE SUMMARY We present the case of a 24-year-old female who was diagnosed with IgA nephropathy due to significant proteinuria and mild renal impairment.Pathologically,she exhibited focal proliferative glomerulonephritis.Treatment with angiotensin II receptor blocker,hormones,and mycophenolate mofetil did not lead to a significant improvement in her condition.However,upon the addition of telitacicept,the patient’s renal function recovered and her proteinuria rapidly reduced.Hormones were swiftly tapered and discontinued,with no occurrence of severe infections or related complications.CONCLUSION Telitacicept combined with hormones and mycophenolate mofetil may be a safe and effective induction therapy for IgA nephropathy.

The Beneficial Effect of 3-Month-Induction Therapy with Corticosteroids and Mycophenolate Mofetil Followed by Maintenance Therapy with Yearly Rituximab Infusions as Sole Maintenance Therapy in Cryptogenic Chronic Hypersensitivity Pneumonitis

Background: The available data on cryptogenic chronic hypersensitivity pneumonitis (ccHP) indicate an inherited predisposition to disease with triggering autoimmune phenomena. Hence, we evaluated prospectively the role of a new autoimmune regimen in treatment of its severe and progressive disease. Patients and Methods: A total of 9 patients were included in the study. They had criteria for ccHP viz. 1) clinical features of cryptogenic progressive restrictive lung disease, 2) high-resolution computed tomographic pulmonary abnormalities, and 3) bronchoalveolar lavage lymphocytosis (>30%). The regimen consisted of an initial induction phase of 3-month Solumedrol 1 g IV daily for 3 days followed by 1 month of Prednisone (P) 60 mg/day to tapered down to discontinuation by 3rd month. They also had received Mycophenolate mofetil (MMF) 1 g twice daily for 3 months. This stage was followed by a maintenance phase of yearly Rituximab infusions (1 g followed by 1 g 2 weeks later). Results: compared to their previous 6 months deterioration;all patients showed significant improvement in their forced vital volume, diffusion capacity for carbon monoxide, 6-minutes-walk after the induction phase (at 3 months) which improved further at 15 months with Rituximab therapy. Conclusion: After 3-month induction therapy with P and MMF;yearly R treatment is a safe, practical and effective long-term therapy for ccHP.

Effect of Rituximab Versus Mycophenolate Mofetil or Cyclophosphamide as Control in Lupus Nephritis:A Meta-Analysis

Objective:To evaluate the effects of rituximab versus mycophenolate mofetil or cyclophosphamide as control in lupus nephritis by meta-analysis.Methods:A systematic search was carried out up to January 2022,obtaining 7 studies involving 645 participants with lupus nephritis at the commencement of the investigation;198 of them were treated with rituximab,while 447 were treated with mycophenolate mofetil or cyclophosphamide.We determined the odds ratio(OR)and mean difference(MD)with 95%confidence index(CI)to compare rituximab’s efficacy to that of mycophenolate mofetil or cyclophosphamide as control in lupus nephritis using random-or fixed-effects model by dichotomous or continuous techniques.Results:The rituximab group showed significantly higher complete renal remission rate(OR=2.52;95%CI 1.30-4.91,P=0.006)and total renal remission rates(OR=2.22;95%CI 1.36-3.63,P=0.001)than the control group.However,there was no significant difference in terms of end Systemic Lupus Erythematosus Disease Activity Index(SLEDAI)score(MD-1.16;95%CI-2.88-0.57,P=0.19),proteinuria(MD-0.31;95%CI-0.70-0.09,P=0.013),and serum creatinine(MD 0.01;95%CI-0.04-0.07,P=0.64)between the rituximab group and the control.Conclusion:Rituximab exhibited significantly greater complete renal remission rate and total renal remission rates,with no significant difference in terms of shorter-end SLEDAI,proteinuria,and serum creatinine,compared with the control in individuals with lupus nephritis.

Mycophenolate mofetil for drug-induced vanishing bile duct syndrome

Amoxicillin/clavulanate is associated with liver injury, mostly of a cholestatic pattern. While outcomes are usually benign, progression to cirrhosis and death has been reported. The role of immunosuppressive therapy for patients with a protracted course is unclear. We report the case of an elderly patient who developed prolonged cholestasis secondary to amoxicillin/clavulanate. Vanishing bile duct syndrome was confirmed by sequential liver biopsies. The patient responded to prednisone treatment, but could not be weaned off corticosteroids, even when azathioprine was added. Complete withdrawal of both prednisone and azathioprine was possible by using mycophenolate mofetil, an inosine monophosphate dehydrogenase inhibitor. Sustained remission has been maintained for more than 3 years with low-dose mycophenolate mofetil.

Effects of mycophenolate mofetil vs cyclosporine administration on graft survival and function after islet allotransplantation in diabetic rats

AIM: To develop an experimental model of islet allotransplantation in diabetic rats and to determine the positive or adverse effects of MMF as a single agent. METHODS: Thirty-six male Wistar rats and 18 male Lewis rats were used as recipients and donors respectively. Diabetes was induced by the use of streptozotocin (60 mg/kg) intraperitoneally. Unpurified islets were isolated using the collagenase digestion technique and transplanted into the splenic parenchyma. The recipients were randomly assigned to one of the following three groups: group A (control group) had no immunosuppression; group B received cyclosporine (CsA) (5 mg/kg); group C receivedmycophenolate mofetil (MMF) (20 mg/kg). The animalswere killed on the 12th d. Blood and grafted tissues were obtained for laboratory and histological assessment. RESULTS: Median allograft survival was significantly higher in the two therapy groups than that in the controls (10 and 12 d for CsA and MMF respectively vs 0 d for the control group, P＜0.01). No difference in allograft survival between the CsA and MMF groups was found. However,MMF had less renal and hepatic toxicity and allowed weight gain.CONCLUSION: Monotherapy with MMF for immunosu ppression was safe in an experimental model of islet allotransplantation and was equally effective with cyclosporine, with less toxicity.

Effect of low-dose tacrolimus with mycophenolate mofetil on renal function following liver transplantation

AIM: To determine whether low-dose tacrolimus (TAC) combined with mycophenolate mofetil (MMF) is a safe approach to decrease the incidence of chronic kidney disease (CKD) in liver transplantation (LT) recipients. METHODS: We analyzed the medical records of 689 patients who underwent LT between March 1999 and December 2012 in a single Chinese center. Immunosuppression was initiated with a calcineurin inhibitor (TAC or CSA) and prednisone with or without MMF. CKD is defined by the glomerular filtration rate (GFR), estimated by an abbreviated Modification of Diet in Renal Disease formula, < 60 mL/min per 1.73 m(2) for at least 3 consecutive months after LT. Individuals with TAC trough concentrations <= 8 ng/mL at 3 mo after LT were defined as the low-dose group. The incidence of CKD within 5 years was compared between the TAC group and the CSA group, as well as between four subgroups (low-dose and high-dose TAC groups with or without MMF). RESULTS: No difference regarding the occurrence of pre-LT renal dysfunction or that of post-LT rejection was found between the TAC and CSA groups or between the four subgroups. With a definition of GFR < 60 mL/min per 1.73 m(2), the overall incidence of CKD was significantly higher in the CSA group than in the TAC group. The incidence of CKD in the low-dose TAC + MMF group (7.7%) was significantly lower than that observed in the low-dose TAC group (15.9%), high-dose TAC group (24.6%) and high-dose TAC + MMF group (18.5%). The cumulative 1-, 3- and 5-year incidence rates of CKD were 12.7%, 14.5% and 16.7%, respectively. The cumulative 5-year survival rates were 61.7% and 82.2% in patients with or without CKD, respectively. CONCLUSION: In LT patients, the choice of immunosuppressive therapy appears to affect renal function and patient survival. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.

Cyclosporine A, FK-506, 40-0-[2-hydroxyethyl]rapamycin and mycophenolate mofetil inhibit proliferation of human intrahepatic biliary epithelial cells in vitro

AIM： To investigate the effect of cyclosporine A （CsA）, FK-506, and mycophenolate mofetil （MMF） and 40-0-[2- hydroxyethyl]rapamycin （RAD） on proliferation of human intrahepatic biliary epithelial cells （BECs） in vitro.METHODS： BECs were isolated from six human liver tissuespecimens with the immunomagnetic separation method and treated with different concentrations of CsA, FK-S06, RAD, and MMF in vitro. Proliferation of the cells was measured by MTT assay at 24 and 48 h after treatment, respectively. One-way analysis of variance was used to analyze the results. Expression of CK 19 in BECs was monitored by flow cytometry and Western blot.RESULTS： Six lines of BECs were established. They survived for 4-18 wk in vitro. Flow cytometry analysis showed that these cells always expressed CK19. CsA, FK-506, RAD, and MMF inhibited proliferation of BECs in a dose-dependent manner. The lowest concentration of CsA, FK-506, RAD, and MMF to inhibit proliferation of BECs （P〈0.05） was 500, 100, 0.25, and 100 pg/L, respectively. However, the expression of CK19 by BECs was not changed.CONCLUSION： CsA, FK-506, RAD, and MMF have an antiproliferative effect on human intrahepatic BECs in vitro, while RAD has the strongest growth-inhibitory effect. Their possible effects on liver regeneration and bile duct injury in transplant patients should be further investigated.

Effects of Mycophenolate Mofetil on Renal Interstitial Fibrosis after Unilateral Ureteral Obstruction in Rats

To investigate the effects of mycophenolate mofetil (MMF) on the process of renal interstitial fibrosis,unilateral ureteral obstruction (UUO) model was established in rats Twenty Sprague-Dawley rats underwent UUO and received vehicle ( n =10) or MMF (20 mg kg -1 d -1 , by daily gastric gavage, n= 10) during a period of 5 days following surgery, and the additional 10 rats were served as sham-operated group The rats were killed 5 days after surgery Immunohistochemistry was performed on renal tissue for proliferating cell nuclear antigen (PCNA), α-smooth muscle actin (α-SMA) and type Ⅰ and Ⅲ collagen (colⅠ, colⅢ) Histological studies were also done by MASSON staining Five days after surgery, proliferating cells in tubules, interstitium as well as interstitial myofibroblast (MyoF) infiltration and interstitial colⅠ, colⅢ deposition were all significantly reduced by MMF treatment MMF also alleviated the histological changes of UUO rats These results suggested that the reduction of interstitial MyoF infiltration may be an important event by which MMF prevents renal injury caused by UUO and MMF could be used to limit the progression of renal fibrosis

Mycophenolate mofetil for maintenance of remission in steroid-dependent autoimmune pancreatitis

Systemic corticosteroids represent the standard treatment for autoimmune pancreatitis with IgG4-associated cholangitis.For steroid-dependent disease,azathioprine has been used for maintenance of remission.Mycophenolate mofetil has been used for transplant immunosuppression and more recently for autoimmune hepatitis;however,there are no case reports to date on the use of mycophenolate mofetil in adult patients with autoimmune pancreatitis.A patient with IgG4-mediated autoimmune pancreatitis and IgG4-associated cholangitis refractory to steroids and intolerant of azathioprine was treated with mycophenolate mofetil,which inhibits de novo guanosine synthesis and blockade of both B and T lymphocyte production.Introduction of mycophenolate mofetil and uptitration to 1000 mg by mouth twice daily over a treatment period of 4 mo was associated with improvement in the patient's energy level and blood glucose control and was not associated with any adverse events.The patient was managed without a biliary stent.However,there was a return of symptoms,jaundice,increase in transaminases,and hyperbilirubinemia when the prednisone dose reached 11 mg per day.In the first report of mycophenolate mofetil use in an adult patient with IgG4-associated autoimmune pancreatitis and IgG4-associated cholangitis,the introduction of mycophenolate mofetil was safe and well-tolerated without adverse events,but it did not enable discontinuation of the steroids.Mycophenolate mofetil and other immunomodulatory therapies should continue to be studied for maintenance of remission in the large subset of patients with refractory or recurrent autoimmune pancreatitis.

Inhibitory effect of mycophenolate mofetil on human hepatocellular carcinoma cell line HepG-2

To investigate the inhibitory effect of mycophenolate mofetil on human hepatocellular carcinoma cell line HepG-2. Methods： HepG-2 cells were cultured in the presence of the different concentrations of mycophenolate mofetil in vitro. MTT assay was used to analyze the inhibition of cell viability conferred by mycophenolate mofetil. Cell apoptosis was observed using Hoechst33258 staining, and the percentage of HepG-2 cells at different cell cycles was determined through flow cytometry. The ability of cell adhesion was evaluated by in vitro adhesion assay. Gene expressions of factors （ICAM-1 and VCAM-1） were detected by RT-PCR. Results： Mycophenolate mofetil significantly inhibited the growth of HepG-2 cells by inducing the apoptosis of cells and this drug also inhibited the adhesion of HepG-2 cells in a dose-dependent manner. Marked morphological changes characterized in cell apoptosis were demonstrated through Hoechst33258 staining. In addition, mycophenolate mofetil decreased the proportion of S phase cells and increased that of G0/G1 phase cells. [^3H]-Thymidine uptake assay indicated that the application of mycophenolate mofetil at different concentrations significantly inhibited the cell proliferation. RT-PCR identified the expression levels of ICAM-1 and VCAM-1 genes in liver cancer cells after cultured for 72 h with different concentrations of drug. An inverse relationship was found between the expressions of ICAM-1 and VCAM-1 and drug concentrations. Conclusion： Mycophenolate mofetil has remarkable inhibitory effect on hepatocarcinoma HepG-2 cells.

TWO-YEAR OBSERVATION OF A RANDOMIZED TRIAL ON TACROLIMUS-BASED THERAPY WITH WITHDRAWAL OF STEROIDS OR MYCOPHENOLATE MOFETIL AFTER RENAL TRANSPLANTATION

Objective To evaluate the safety and feasibility of steroid or mycophenolate mofetil （MMF） withdrawal from tacrolimus-based immunosuppressant regimen in renal allograft recipients. Methods A cohort of 45 patients following cadaveric renal allograft transplantation were randomly divided into 3 groups based on the regimen of combination of tacrolimus, steroid, and MMF： triple therapy group, steroid withdrawal group, and MMF withdrawal group. During 2 years, survival of patients and allografts, clinical acute rejection, adverse events, hepatic and renal allograft function, and blood lipids were monitored to evaluate the safety and feasibility of steroid or MMF withdrawal after renal transplantation. Results During two-year observation, steroid or MMF was successfully withdrawn from immunosuppressant regimen based on tacrolimus without any clinical acute rejection renal allografts kept excellent function. Some adverse events among groups. Patient and graft survival rates were 100% and all the occurred and there were no significant differences Conclusion Withdrawal of steroid or MMF in low-immunological-risk renal allografts treated with tacrolimus-based immunosuppressant regimen can be achieved with no increased risk of acute rejection.

Correlation of abnormal histology with endoscopic findings among mycophenolate mofetil treated patients

To describe all abnormal histological findings and their associated endoscopic presentation in patients using mycophenolate mofetil (MMF). METHODSA retrospective review of all individuals prescribed MMF within 6 mo of a colonoscopy or flexible sigmoidoscopy between 07/2009 and 09/2015 was performed within Northwell Health system. Records were analyzed for age, gender, procedure indication, MMF indication, and both gross and microscopic findings. Only reports with abnormal histology were included. RESULTSOne hundred and eighty-four procedures from 170 patients were found, of which 39 met inclusion criteria. Fifty-one point three percent were female. MMF was used for solid organ transplant in 71.8%. Diarrhea was the indication for 71.8% of colonoscopies. Fifty-nine percent of reports revealed gross and microscopic abnormalities while 41.0% had only microscopic findings. Only 11 patients’ reports (28.2%) indicated a specific histopathology of MMF colitis. Among the entire group, only 23.1% of abnormal histology was isolated proximal to the splenic flexure. CONCLUSIONOur results demonstrate a high rate of left sided disease and microscopic findings without gross mucosal abnormalities among patients using MMF. Also, a broader definition of MMF-colonopathy may be appropriate, with a majority of our abnormal histology falling outside of the more narrowly defined MMF-colitis category. Given the high frequency of isolated microscopic abnormalities and distal disease, sigmoidoscopy with random biopsies may be an appropriate, less invasive initial endoscopic examination in selected MMF patients.

Protective Effect of Mycophenolate Mofetil(MMF) Against Short-term Acute Rejection of Kidney Transplant

To observe the protective effect of MMF against short term(3 months) acute rejection of renal transplantion. 112 patients undergone renal transplantation were randomly divided into two groups: MMF group (2.0 g/d) and azathioprine group. Patients in both groups received cyclosporine A (CsA) and steroid hormone treatment in the same way. In three months time, 10/60 cases in the MMF treated group showed acute rejection with an acute rejection rate of 16.6%. 22/52 patients of the AZA group had acute rejection with a rejection rate of 41.5%. The difference between the two groups is significant (P<0 01). Side effects manifested in MMF group includereduction of blood white cell count and platelet count (5 cases) and diarrhea (3 cases). They resume recovery after reduction of the dosage of or stoppage of MMF. Both hepatic renal functions are not affected. In AZA group, liver function is damaged in 9 patients. MMF is effective in the prevention or reduction of short term acute rejection of transplants. Its side effects are mild and reversible.

Influence of mycophenolate mofetil (MMF) upon thematuration and allo-stimulatory activity of cultured progenitors of dendritic cells and the effectson the tolerance induction in allograft recipients

To investigate the influence of mycophenolate mofetil (MMF) upon the maturation and the allo-stimulatory activity of cultured progenitors of dendritic cells (DCp), and to evaluate the effects of the pre-treated dentritic cells of recipients with MMF on the tolerance induction as well as its possible mechanism, GM-CSF and MMF were added to the in vitro cultured progenitor cells, and the immuno-phenotypical analysis was performed by means of flow cytometry. The secretion of IL-12 was detected by ELISA and the stimulatory activities of DCp on allogeneic T cells were observed by mixed lymphocyte reaction. Twenty-four C57BL/6 mice were divided into 3 groups (each with 8 mice), in which group A of mice accepted allografts of heart from BALB/c mice, group B of mice had received untreated DCp from donors of BALB/c mice 7 days before transplantation, and C57BL/6 mice in group C were treated by injection with MMF-treated allografts of heart from BALB/c mice 7 days before transplantation. The survival times of allografts and the changes of the cytokine levels in sera of the recipient mice were observed after transplantation. The experimental results showed that MMF could significantly inhibit the expressions of the co-stimulatory molecules CD80 and CD86 on DCs and the secretion of IL-12 and the allo-stimulatory activities of DCs were also markedly inhibited. The survival times of allografts in group B of mice were longer than those in group A, while the group C showed the longest survival times of allografts, with a marked reduction in the production of the Th1 type cytokines. It is evident that MMF has a suppressive effect on the maturation and allo-stimulatory activities of the cultured dendritic cell progenitors, thus leading to a donor specific tolerance in heart-transplanted recipients.

Effects of mycophenolate mofetil,valsartan and their combined therapy on preventing podocyte loss in early stage of diabetic nephropathy in rats

Background Podocyte has inflammatory role in the development of diabetic nephropathy （DN）. Mycophenolate mofetil （MMF）, an anti-inflammatory agent, can suppress macrophage infiltration and reduce renal injury in streptozotocin-induced diabetic rats. Angiotensin II receptor blocker （ARB）, another renal protecting agent, can decrease podocyte loss in DN. In this study, we detected the expression levels of monocyte chemoattractant protein-1 （MCP-1） and nephrin to evaluate podocyte＇s role in inflammatory reaction in DN, observe and compare the effect of MMF alone and in combination with valsartan, on preventing podocyte loss in streptozotocin （STZ） induced diabetic rats. Methods Diabetic model was constructed in uninephrectomized male Wistar rats by single peritoneal injection of STZ （65 mg/kg）. The successfully induced diabetic rats were randomly divided into four groups： diabetes without treatment group （DM）, valsartan treated group （DMV）, MMF treated group （DMM）, and combined therapy group （DMVM）. Normal rats of the same sibling were chosen as control （NC）. At the end of the 8th week, serum biochemistry, 24-hour urinary protein （LIP） and the ratio of kidney weight/body weight （RWK/B） were measured. The rats were sacrificed for the observation of renal histomorphology through light and electron microscope. Nephrin, desmin and MCP-1 levels were detected by semi-quantitative immunohistochemical assays. Real-time quantitative PCR was used to detect the mRNA levels of nephrin and MCP-1. Results Compared with group NC, serum glucose level, 24-hour LIP and RWK/B in group DM were significantly higher （P〈0.01）, and the nephrin mRNA level in DM group was significantly lower （P〈0.05）. The nephrin mRNA expression levels in group DMV, DMM and DMVM were all higher than that of DM group （P〈0.05） and no significant differences were found among the three treatment groups （P〉0.05）. Treatment with MMF, valsartan or their combination could significantly decrease the 24-hour LIP and RWK/B, and suppress glomerulosclerosis and interstitial fibrotic lesions in diabetic rats. In diabetic rats, the high expressions of desmin and MCP-1 in kidney were suppressed by valsartan, MMF or their combination. Conclusions Podocytes are involved in the inflammatory reaction of diabetic rats. MMF could suppress MCP-1 and desmin expression, enhance nephrin expression, and attenuate proteinuria in diabetic rats. The combined therapy of valsartan and MMF did not show any superiority over monotherapies on renal protection. MMF may have renoprotective effect in early stages of diabetic nephropathy through preventing podocytes loss and anti-inflammatory activity.

Retrospective study of mycophenolate mofetil treatment in IgA nephropathy with proliferative pathological phenotype

Background Mycophenolate mofetil （MMF） and cyclophosphamide （CTX） are widely used in treating various kidney diseases.However,whether they are effective and which one is better for treating IgA nephropathy patients with proliferative pathological phenotype in renal diseases,such as endocapillary proliferation,cellular crescents,and/or capillary loops fibrinoid necrosis is still unknown.We,therefore,initiated a study to compare the effects of MMF and CTX in treating IgA nephropathy with the above pathological lesions.Methods One hundred and nineteen patients with IgA nephropathy who had at least one of the three aforementioned lesions were enrolled.All patients were treated with prednisone; 48 patients received prednisone only （Pred group）,40 received MMF and prednisone （MMF ＋ Pred group）,and 31 were treated with CTX and prednisone （CTX ＋ Pred group）.The median time of follow-up was 30 months （maximum：96 months）.The primary endpoint was defined as renal survival.The incidence of remission of proteinuria was the secondary endpoint.Results Serum creatinine in all groups declined significantly at different follow-up times （P=0.002）,and the differences among the three groups were significant （P＜0.001）.At 24 months of follow-up,the decline rates were 12.35％,32.95％,and 24.14％ in the Pred,MMF ＋ Pred,and CTX ＋ Pred groups respectively.For urine protein excretion,the decline rates were 49.12％ （Pred）,73.67％ （MMF ＋ Pred）,and 63.53％ （CTX ＋ Pred） respectively at 24 months of follow-up.The differences among the three groups were not significant （P=0.714）.Renal survival （the primary endpoint） was significantly different （P=0.027）; however,the sencondary endpoint was similar for all the three groups （P=0.100）.Conclusions For IgA nephropathy patients with endocapillary proliferation,cellular crescents,and/or fibrinoid necrosis of capillary loops,prednisone combined with MMF was more effective in lowering the serum creatinine than with CTX.Combined MMF and orednisone treatment led to a better renal survival compared to that of prednisone with CTX.

Mycophenolate mofetil plus prednisone for inducing remission of Henoch-Sch?nlein purpura nephritis: a retrospective study

Objective： The treatment of Henoch-Schonlein purpura （HSP） with moderate proteinuria remains con- troversial. We retrospectively analyzed the efficacy of immune suppressants, with a particular emphasis on myco- phenolate mofetil （MMF）. Methods： Ninety-five HSP patients with moderate proteinuria （1.0-3.5 g/24 h） after at least three months of therapy with angiotensin-converting enzyme inhibitor （ACEI） or angiotensin receptor blocker （ARB） were divided into three groups： an MMF group （n=33） that received MMF 1.0-1.5 g/d combined with prednisone （0.4-0.5 mg/（kg.d））, a corticosteroid （CS） group （n=31） that received full-dose prednisone （0.8-1.0 mg/（kg.d））, and a control group （n=31）. Patients in the MMF and CS groups continued to take ACEI or ARB at the original dose. The patients in the control group continued to take ACEI or ARB but the dose was increased by （1.73±0.58）-fold. The patients were followed up for 6-78 months （median 28 months）. Results： The baseline proteinuria was higher in the MMF group （（2.1±0.9） g/24 h） than in the control group （（1.6±0.8） g/24 h） （P=0.039）. The proteinuria decreased sig- nificantly in all groups during follow-up, but only in the MMF group did it decrease significantly after the first month. At the end of follow-up, the proteinuria was （0.4±0.7） g/24 h in the MMF group and （0.4±0.4） g/24 h in the CS group, significantly lower than that in the control group （（0.9±1.1） g/24 h）. The remission rates in the MMF group, CS group, and control group were respectively 72.7%, 71.0%, and 48.4% at six months and 72.7%, 64.5%, and 45.2% at the end of follow-up. The overall number of reported adverse events was 17 in the MMF group, 30 in the CS group, and 6 in the control group （P〈0.001）. Conclusions： MMF with low-dose prednisone may be as effective as full-dose prednisone and tend to have fewer adverse events. Therefore, it is probably superior to conservative treatments of adult HSP patients with moderate proteinuria.

Mycophenolate mofetil affects monocyte Toll-like receptor 4 signaling during mouse renal ischemia/reperfusion injury

Background Mycophenolate mofetil （MMF） has been used to prevent transplant rejection for many years and has been shown to have protective effects against renal failure. The objective was to investigate the effect of MMF on monocyte Toll-like receptor 4 （TLR4） signaling in the early stages of renal ischemia/reperfusion injury （IRI） of mice. Methods Sixty BALB/C mice were randomly divided into two groups： an IRI group, in which renal IRI was induced by clamping the renal pedicles for 45 minutes, and an MMF group, in which MMF was given （40 mg.kg-l.d-1, intraperitoneally） from 2 days before renal IRI. The plasma creatinine level and renal tissue damage of each group mice were observed 6, 12, 24, and 48 hours after reperfusion. The concentration of plasma high-mobility group box 1 （HMGB-1） （TLR4 ligand）, interleukin 6 （IL-6）, monocyte chemoattractant protein-1 （MCP-1）, and tumor necrosis factor a （TNF-cc） and the expression of TLR-4 on monocytes were determined. Results The plasma creatinine concentration in the MMF group was lower compared to the IRI group （after reperfusion of 6, 12, 24, or 48 hours, P 〈0.05）. Pathological analysis showed that the renal damage was slighter, TLR-4 expression was reduced （after reperfusion of 6, 12, 24, or 48 hours, P 〈0.05）, and the concentration of cytokines in the plasma was lower （P 〈0.05） in the MMF group. No differences in the concentrations of HMGB-1 were observed （P 〉0.05）. Conclusion Monocyte TLR4 signaling is important in the early stage of kidney IRI, but MMF can inhibit it and improve renal function.

Mizoribine versus mycophenolate mofetil or intravenous cyclophosphamide for induction treatment of active lupus nephritis

Background Lupus nephritis （LN） is one of the most serious manifestations of systemic lupus erythematosus.Although there have been substantial improvements in LN treatment over the last decade,the outcome remains unoptimistic in a considerable percentage of patients.The aim of this study was to evaluate the efficacy and safety of mizoribine （MZR）,a novel selective inhibitor of inosine monophosphate dehydrogenase,as induction treatment for active LN in comparison with mycophenolate mofetil （MMF） and intravenous cyclophosphamide （CYC）.Methods Ninety patients with active LN were observed.Thirty patients were given MZR orally at the dose of 300 mg every other day.Thirty patients took MMF at 2 g per day in two divided doses.Thirty patients received CYC intravenously 0.5 g every 2 weeks.Therapeutic effects and adverse events （AEs） were evaluated at the end of 24-week treatment.Oneway analysis of variance （ANOVA） followed by Dunn＇s test was applied to compare the difference among the groups.For comparing categorical data between two groups,χ^2 test was employed.Results Early responses at week 12 were achieved by 73.3%,90.0%,and 96.7% in MZR,MMF,and CYC groups,respectively.There was no significant difference in the complete remission rates （22.7%,24.0%,and 25.0%,respectively） or overall response rates （68.2%,72.0%,and 75.0%,respectively） among the three groups at week 24.The most prominent drop-down of Systemic Lupus Erythematosus Disease Activity Index scores was observed in MMF or CYC group,and the decline of health assessment questionnaire scores in MZR or MMF group was more prominent than that in the CYC group at week 12.Serum complement 3 （C3） or C4 levels were elevated in all groups after the treatments.CYC was more effective in inhibiting anti-double-stranded DNA antibody,while MZR was more effective in inhibiting antinuclear antibody.The incidences of AEs in patients treated with CYC were significantly higher than those in patients treated with MZR or MMF （24.2% for CYC vs.3.3% for MZR,and 2.6% for MMF,P=0.01）.Conclusions MZR is well tolerated and has an effect similar to MMF in the induction therapy of active LN.MZR may serve as an alternative approach for LN patients.